Abstract

Wnt signalling plays essential roles during embryonic development and is known to be mis-regulated in human disease. There are many molecular mechanisms that ensure tight regulation of Wnt activity. One such regulator is the heparan sulfate specific 6-O-endosulfatase, Sulf1. Sulf1 acts extracellularly to modify the structure of heparan sulfate (HS) chains to affect the bio-availability of Wnt ligands. Sulf1 could, therefore, influence the formation of Wnt signalling complexes to modulate the activation of both canonical and non-canonical pathways. In this study we use well established assays in Xenopus to investigate the ability of Sulf1 to modify canonical and non-canonical Wnt signalling. In addition, we model the ability of Sulf1 to influence morphogen gradients using fluorescently tagged Wnt ligands in ectodermal explants. We show that Sulf1 over-expression has ligand specific effects on Wnt signalling: differentially affecting membrane accumulation and extracellular levels of tagged ligands, and inhibiting the activity of canonical Wnt8a while enhancing the activity of non-canonical Wnt11b.

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